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Early decrease in the podocalyxin to synaptopodin ratio in urinary Fabry podocytes.

Hernán Trimarchi1, Romina Canzonieri2, Cristian Costales-Collaguazo3

  • 1Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.

Clinical Kidney Journal
|February 13, 2019
PubMed
Summary

Fabry disease patients show increased podocyturia, indicating potential glycocalyx damage. Enzyme replacement therapy may be initiated late, as treated patients exhibit higher proteinuria.

Keywords:
Fabry nephropathypodocalyxinpodocytepodocyturiasynaptopodin

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Area of Science:

  • Nephrology
  • Glomerular Diseases
  • Podocyte Biology

Background:

  • Podocyturia is an early indicator of kidney damage in Fabry nephropathy, potentially leading to glomerulosclerosis.
  • The podocyte glycocalyx, specifically podocalyxin, is investigated as a marker of damage in glomerulopathies.

Purpose of the Study:

  • To investigate glycocalyx podocalyxin in urinary detached podocytes in Fabry nephropathy patients.
  • To compare podocalyxin expression with cytoplasmic synaptopodin in detached podocytes.

Main Methods:

  • Cross-sectional study of 68 individuals (20 controls, 48 Fabry patients: 15 untreated, 33 treated).
  • Assessed podocyturia via immunofluorescence, analyzing podocyte subpopulations.
  • Measured urinary protein/creatinine ratio (UPCR), eGFR, and lyso-Gb3 levels.

Main Results:

  • Fabry patients exhibited higher podocyturia than controls.
  • Treated Fabry patients had higher UPCR than untreated patients; no differences in podocyturia, eGFR, or lyso-Gb3.
  • While controls showed synaptopodin/podocalyxin colocalization, 73% of Fabry patients had only synaptopodin-positive cells.

Conclusions:

  • Fabry patients present with increased podocyturia and likely glycocalyx damage (podocalyxin).
  • Higher proteinuria in treated patients suggests late initiation of enzyme replacement therapy (ERT).
  • Podocalyxin assessment alone may underestimate podocyturia; further research on podocyte glycocalyx damage is warranted.